Congenital folate malabsorption.
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Biomedical subjects
Publications and source records attributed to N Colman.
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Dichloroacetate demonstrates low grade mutagenicity in the Ames Salmonella/mammaltan microsome mutagenicity test. This evidence of probable carcinogenicity must be considered in any proposed use of dichloroacetate or of preparations of pangamic acid (trade-named "vitamin B15") CONTAINING DICHLOROACETATE.
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The current study presents evidence that all human serum contains a class of high-affinity folate binders (KA=2.8 X10(10 liters/mole), which migrate as a single peak on gel filtration. Failure of previous studies to detect this characteristic in all but a minority of subjects is attributable to its variable, often total, saturation. Direct measurement of the total folate binding capacity (TFBC) has been made possible by dissociation of endogenous folate-binder complexes at acid pH, removal of free folate by coated charcoal, and radiofolate tagging. This procedure does not appear to significantly denature the binders, which release and rebind similar quantities of 3H-PGA. In 20 normal subjects, TFBC ranged from 100 to 325 pg/ml (mean+/-SE = 174+/-16), and was always at least 33% saturated. In three clinical conditions, all associated with elevated unsaturated folate binding capacity, three different patterns emerged when TFBC was also measured. Uremic subjects had significantly elevated mean TFBC with normal saturation. In cirrhotic subjects, mean TFBC approximated normal, but saturation was significantly decreased. In pregnancy, two groups were seen: one with increased TFBC and the other with a normal TFBC, some of whom had decreased saturation. Lactobacillus casei serum folate level was about 30 times greater than the TFBC; there was no correlation between the two measurements.
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Tissue deficiency of folic acid, as measured by a red cell folate level below 150 ng. per milliliter, was present in 16 per cent of 110 sequential pregnant women at the time of their first prenatal visit to a municipal clinic. A further 14 per cent of subjects had red cell folate levels in the range "suggestive but not conclusive for tissue folate depletion" (150 to 199 ng. per milliliter). All of the subjects were from low-income families in New York City and most were black or of Puerto Rican origin. Serum folate levels showed good general correlation with red cell folate but were of less value as a diagnostic test, since they were below the lower limit of normal in 64 per cent of subjects, including many subjects who did not yet have low tissue folate. In contrast to their value in other folate deficiency states, neutrophil lobe counts showed no correlation with serum or red cell folate levels in pregnancy and thus appeared of little diagnostic value in pregnancy. It is suggested that surveys of folate deficiency in other pregnant population groups in the United States be carried out. These results support the recommendations of the Committee on Maternal Nutrition and the Committee on Dietary Allowances of the Food and Nutrition Board, National Research Council (U.S.A.) that folic acid supplements (200 to 400 mug per day) should be taken throughout pregnancy.
The serum vitamin B12 level falls progressively during pregnancy, when measured either by microbiologic assay or by a radioisotope dilution technique. The concentration of the vitamin assayed by radioisotope dilution was consistently higher than the value obtained by microbiologic assay. This discrepancy was greatest in early pregnancy and decreased as the duration of pregnancy increased. These results add further evidence to the hypothesis that changes in serum binders for vitamin B12 are of major significance in the pathogenesis of the observed fall in serum levels of the vitamin during pregnancy.
The absorption of folic acid from maize, rice and bread fortified with pteroylglutamic acid was compared with that of an aqueous solution of pteroylglutamic acid in the same subjects. Feeding fortified maize and rice produced similar increments in folic acid concentration, which were approximately half those observed with the pteroylglutamic acid solution. Fortified bread produced a lower increment. Pteroylglutamic acid was found to resist destruction by boiling and baking at temperatures and times used for the conventional preparation of such foods. However, baking for longer periods resulted in a loss of folic acid activity. It is concluded that fortification of staple foods with folic acid may offer a practical adjunct to nutritional programs designed to improve the intake of essential nutrients.